High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.

Abstract

OBJECTIVES:

To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril.

BACKGROUND:

The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect.

METHODS:

In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones.

RESULTS:

At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses.

CONCLUSIONS:

Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.

• Authors: D J van Veldhuisen, S Genth-Zotz, J Brouwer, F Boomsma, T Netzer, A J Man In 'T Veld, Y M Pinto, K I Lie, H J Crijns
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 32 Issue 7 Pg. 1811-8 (Dec 1998) ISSN: 0735-1097 [Print] United States
• PMID: 9857856 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Imidazoles
• Imidazolidines
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• imidapril

Topics

• Adult
• Aged
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Atrial Natriuretic Factor (blood)
• Double-Blind Method
• Exercise Test
• Female
• Heart Failure (blood, drug therapy)
• Humans
• Imidazoles (pharmacology, therapeutic use)
• Imidazolidines
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Renin-Angiotensin System (drug effects)